Diverse lamin-dependent mechanisms interact to control chromatin dynamics. Focus on laminopathies

Nucleus. 2014 Sep-Oct;5(5):427-40. doi: 10.4161/nucl.36289.

Abstract

Interconnected functional strategies govern chromatin dynamics in eukaryotic cells. In this context, A and B type lamins, the nuclear intermediate filaments, act on diverse platforms involved in tissue homeostasis. On the nuclear side, lamins elicit large scale or fine chromatin conformational changes, affect DNA damage response factors and transcription factor shuttling. On the cytoplasmic side, bridging-molecules, the LINC complex, associate with lamins to coordinate chromatin dynamics with cytoskeleton and extra-cellular signals. Consistent with such a fine tuning, lamin mutations and/or defects in their expression or post-translational processing, as well as mutations in lamin partner genes, cause a heterogeneous group of diseases known as laminopathies. They include muscular dystrophies, cardiomyopathy, lipodystrophies, neuropathies, and progeroid syndromes. The study of chromatin dynamics under pathological conditions, which is summarized in this review, is shedding light on the complex and fascinating role of the nuclear lamina in chromatin regulation.

Keywords: Emery-Dreifuss muscular dystrophy; Hutchinson-Gilford progeria; LADs; chromatin; familial partial lipodystrophy; laminopathies; lamins; mandibuloacral dysplasia; nuclear envelope proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acro-Osteolysis / genetics
  • Acro-Osteolysis / pathology
  • Chromatin / genetics*
  • Chromosome Structures / genetics
  • Cytoskeleton / genetics*
  • Humans
  • Lamin Type A / genetics*
  • Lamin Type B / genetics*
  • Lipodystrophy / genetics
  • Lipodystrophy / pathology
  • Lipodystrophy, Familial Partial / genetics
  • Lipodystrophy, Familial Partial / pathology
  • Mandible / abnormalities
  • Mandible / pathology
  • Muscular Dystrophy, Emery-Dreifuss / genetics
  • Muscular Dystrophy, Emery-Dreifuss / pathology
  • Mutation
  • Nuclear Envelope / genetics
  • Progeria / genetics
  • Progeria / pathology

Substances

  • Chromatin
  • Lamin Type A
  • Lamin Type B

Supplementary concepts

  • Mandibuloacral dysplasia with type A lipodystrophy